Efficient Hydrophilic Small Molecule Delivery To Retinal Cell Lines Using Solid Lipid Nanoparticle Containing Gel Core

In this study, we developed a novel solid lipid nanoparticle (SLN) formulation for drug delivery of small hydrophilic cargo to the retina. The new formulation, based on a gel core and compo-site shell, allowed up to two times increase in the encapsulation efficiency. The type of hydro-phobic polyester used in the composite shell mixture affects the particle surface charge, colloidal stability, and cell internalization profile. We validated the SLN capability as a drug delivery system by performing encapsulation of a hydrophilic neuroprotective cyclic guanosine mono-phosphate analogue, previously demonstrated to hold retinoprotective properties, and the best formulation resulted in particles with size of plus/minus 250nm, anionic charge > -20 mV, and an encapsu-lation efficiency value of plus/minus 60%, criteria that are suitable for retinal delivery. In vitro studies using ARPE-19 and 661W retinal cell lines revealed a relatively low SLN toxicity, even when high par-ticle concentration was used. More importantly, SLN could be uptaken by the cells and the re-lease of the hydrophilic cargo in the cytoplasm was visually demonstrated. These findings sug-gest that the newly developed SLN with a gel core and composite polymer/lipid shell holds all characteristics suitable for drug delivery of small hydrophilic active molecules into retinal cell.